The aim of this project is to understand biochemical mechanisms of action of vitamin A. The phosphorylated vitamin, retinyl phosphate, acts in biological membranes as a glycosyl carrier and appears to regulte the biosynthesis of glycoproteins. Subcellular fractions from rat liver were analyzed for the topological distribution of the mannosyl transferases which glycosylate the lipid intermediates retinyl phosphate and the polyisoprenoid derivative dolichyl phosphate. The glycosyl transferases as well as the substrates retinyl phosphate and dolichyl phosphate were found localized mainly in the endoplasmic reticulum of rat liver. The activity of retinyl phosphate as glycosylating agent was lost upon hydrogenation of the four double bonds in the side chain of the molecule. This procedure also abolished growth promoting activity, but it did not affect glycosyl acceptor activity. Retinyl phosphate was found to function in a direct glycosylation of endogenous glycoproteins, whereas dolichyl phosphate transferred mannose to oligosaccharide-lipids. The condition of nutritional vitamin A deficiency caused a depletion of liver retinyl palmitate and retinyl phosphate pools at the same time as dolichyl phosphate increased four-fold. Post nuclear membranes from transplanted and primary rat hepatoma tissue were in a status of retinyl palmitate and retinyl phosphate depletion, whereas their dolichyl phosphate content was not altered significantly from that of the host rat liver. Vitamin A depletion of the tumor tissue did not appear related to cell division rates, inasmuch as hepatectomy failed to have a considerable effect on retinyl palmitate and retinyl phosphate content of regenerating liver at 24 and 48 hours. It should be considered that the vitamin A deficiency condition of the tumor cell may be either the consequence of cell selection during carcinogenesis or a permissive condition for the development of the tumor from initiated cells.